Quantification of Myocardial Fibrosis in Aortis Stenosis

Official title

Myocardial Fibrosis With High Frame Rate Echocardiography in Patients With Aortic Stenosis - A Follow-up Study

Overview

This study is a long term follow-up of patients that were included as part of a previous study (NCT03422770), where patients with aortic stenosis and healthy controls went through echocardiography, cardiac MRI, long-term ECG-recording, blood tests and quality of life assessment. Echocardiography included high frame ultrasound for detection of natural mechanical waves, and the measured speed of these waves were used as a marker of the extent of myocardial fibrosis. Up to five years have now passed since inclusion at baseline, and a proportion of the patients in the cohort have undergone aortic valve replacement at some point. In this study, the investigators will repeat the cardiac imaging (echocardiography and cardiac MRI), ECG and blood test, to assess long-term changes in myocardial fibrosis in aortic stenosis patients.

Detailed description

High frame rate ultrasound with quantification of myocardial mechanical wave velocities provides a new approach to evaluation of myocardial stiffness.

Principle: An elastic medium (the left ventricle) is incited by a force (naturally occuring mechanical wave generated by atrial contraction and/or closure of mitral and aortic valve), and the resulting oscillation wave propagates through the medium with a speed that depends only on the density and stiffness of the medium. If the density of the medium is known, measuring the propagation velocity of the wave is the same as measuring the stiffness of the medium.

There is a lack of longitudinal data in this research area. A follow-up study of the described cohort, will add valuable insight into high frame rate ultrasound as a potential tool to quantify myocardial fibrosis in heart failure patient, and to monitor any changes from baseline.

Interventions

• Diagnostic test High frame rate echocardiography
  Conventional transthoracic echocardiography will be performed, with added 3D-imaging and acquisitions with high frame rate. The data from these patients will be anonymized and transferred for post-hoc analysis in dedicated computer software (GE Vingmed, EchoPac 2.6) and in validated machine learning algorithms.
• Diagnostic test MRI
  Cardiac MRI will be performed. In all patients without contraindications, a gadolinium-based contrast agent will be given.
• Diagnostic test Blood test
  Conventional brachial venous blood samples will be drawn. Hematocrit value {in %} will be used to calculate CMR-derived exttracellular volume (ECV)
• Diagnostic test ECG and Holter-ECG
  ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.
• Diagnostic test 6 min walking test
  6 MWT will be performed, and the findings will be related to findings from CMRI/echocardiography.

Primary outcome measures

• Cardiovascular morbidity [Time frame: 5 year]
• Cardiovascular mortality [Time frame: 5 year]

Secondary outcome measures (9)

• All cause mortality [Time frame: 5 years]
• Time of first re-hospitalization [Time frame: 5 years]
• Cardiac systolic function [Time frame: 5 years]
• Cardiac diastolic function (1 of 5) [Time frame: 5 years]
• Cardiac diastolic function (2 of 5) [Time frame: 5 years]
• Cardiac diastolic function (3 of 5) [Time frame: 5 years]
• Cardiac diastolic function (4 of 5) [Time frame: 5 years]
• Cardiac diastolic function (5 of 5) [Time frame: 5 years]
• Velocity of natural mechanical waves propagating through the myocardium [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Part of the initial cohort that were included in the baseline study
• Still able to undergo protocolled investigations
• Patients: Mild, moderate or severe AS

Exclusion criteria

• Renal insufficiency
• Previously myocardial infarction (ECG, echocardiogram or hospital record)
• Severe valvular heart disease (except patients)
• Other cardiac disease known to cause myocardial fibrosis
• Severe hypertension
• Other medical conditions deterring protocolled investigation and follow-up
• Other medical conditions affecting 5-years prognosis (cancer, pulmonary disease)
• Severely reduced image-quality (echocardiography and MRI)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

Norway · 1 center

• St. Olavs Hosptial — Trondheim

Publications

• Salles S, Espeland T, Molares A, Aase SA, Hammer TA, Stoylen A, Aakhus S, Lovstakken L, Torp H. 3D Myocardial Mechanical Wave Measurements: Toward In Vivo 3D Myocardial Elasticity Mapping. JACC Cardiovasc Imaging. 2021 Aug;14(8):1495-1505. doi: 10.1016/j.jcmg.2020.05.037. Epub 2020 Aug 26. PMID 32861651
• M. Mohajery, S. Salles, T. Espeland, S. Fadnes and L. Lovstakken,
• Espeland T, Wigen MS, Dalen H, Berg EAR, Hammer TA, Salles S, Lovstakken L, Amundsen BH, Aakhus S. Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis. JACC Cardiovasc Imaging. 2024 Feb;17(2):111-124. doi: 10.1016/j.jcmg.2023.07.009. Epub 2023 Sep 6. PMID 37676209

Identifiers

NCT: NCT06571175 · 527717

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗